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Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis

View Article: PubMed Central - PubMed

ABSTRACT

Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.

The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.

The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0.016), neutrophil gelatinase-associated lipocalin (NGAL) (r = 0.320, P = 0.039), microalbumin (r = 0.621, P = 0.003), transferring (r = 0.451, P = 0.040) levels and renal pathological indices scores, especially interstitial inflammation (r = 0.349, P = 0.025) in active lupus nephritis patients. A significant correlation was found between serum and urine PTX3 levels (r = 0.431, P = 0.006). PTX3 staining was mainly observed in tubulointerstitial areas of patients with lupus nephritis, and immunofluorescence study showed that PTX3 could colocalize with fibroblast in interstitium.

Circulating and local PTX3 levels were significantly increased in patients with active lupus nephritis and might be a biomarker for the disease progression, especially of tubulointerstitial injury.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemistry staining for PTX3 in renal specimens of patients with active LN controls (original magnification ×400): (A–C) PTX3 staining in active lupus nephritis patients (the arrow indicating the small vessel). (D) PTX3 staining in lupus nephritis patient with the omission of the PTX3-specific primary antibody. (E) PTX3 staining in IgA nephropathy patients. (F) PTX3 staining in minimal change disease patient. (G) PTX3 staining in normal control.
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Figure 3: Immunohistochemistry staining for PTX3 in renal specimens of patients with active LN controls (original magnification ×400): (A–C) PTX3 staining in active lupus nephritis patients (the arrow indicating the small vessel). (D) PTX3 staining in lupus nephritis patient with the omission of the PTX3-specific primary antibody. (E) PTX3 staining in IgA nephropathy patients. (F) PTX3 staining in minimal change disease patient. (G) PTX3 staining in normal control.

Mentions: The PTX3 expressions in renal tissues were investigated in 35 patients with active lupus nephritis by immunohistochemistry. The PTX3 staining was absent in glomeruli despite the proliferative and inflammatory lesions (Figure 3A). Intense staining for PTX3 was mainly observed in the tubulointerstitial areas of lupus nephritis patients (Figure 3B). In some patients, staining could also be found in small vessels (Figure 3C). The omission of the PTX3-specific primary antibody completely abolished the staining (Figure 3D). PTX3 could be detected in the mesangium of IgA nephropathy patients (Figure 3E), which was consistent with previous study.27 Renal tissues from minimal change disease patients and normal control stained negative for PTX3 (Figure 3F and G). The mean optical density of PTX3 in tubulointerstitium of lupus nephritis was 0.46 ± 0.28 and correlated positively with total renal activity indices score (r = 0.372, P = 0.021), interstitial inflammation (r = 0.369, P = 0.010), and interstitial fibrosis (r = 0.326, P = 0.038) in lupus nephritis group, respectively.


Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis
Immunohistochemistry staining for PTX3 in renal specimens of patients with active LN controls (original magnification ×400): (A–C) PTX3 staining in active lupus nephritis patients (the arrow indicating the small vessel). (D) PTX3 staining in lupus nephritis patient with the omission of the PTX3-specific primary antibody. (E) PTX3 staining in IgA nephropathy patients. (F) PTX3 staining in minimal change disease patient. (G) PTX3 staining in normal control.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Figure 3: Immunohistochemistry staining for PTX3 in renal specimens of patients with active LN controls (original magnification ×400): (A–C) PTX3 staining in active lupus nephritis patients (the arrow indicating the small vessel). (D) PTX3 staining in lupus nephritis patient with the omission of the PTX3-specific primary antibody. (E) PTX3 staining in IgA nephropathy patients. (F) PTX3 staining in minimal change disease patient. (G) PTX3 staining in normal control.
Mentions: The PTX3 expressions in renal tissues were investigated in 35 patients with active lupus nephritis by immunohistochemistry. The PTX3 staining was absent in glomeruli despite the proliferative and inflammatory lesions (Figure 3A). Intense staining for PTX3 was mainly observed in the tubulointerstitial areas of lupus nephritis patients (Figure 3B). In some patients, staining could also be found in small vessels (Figure 3C). The omission of the PTX3-specific primary antibody completely abolished the staining (Figure 3D). PTX3 could be detected in the mesangium of IgA nephropathy patients (Figure 3E), which was consistent with previous study.27 Renal tissues from minimal change disease patients and normal control stained negative for PTX3 (Figure 3F and G). The mean optical density of PTX3 in tubulointerstitium of lupus nephritis was 0.46 ± 0.28 and correlated positively with total renal activity indices score (r = 0.372, P = 0.021), interstitial inflammation (r = 0.369, P = 0.010), and interstitial fibrosis (r = 0.326, P = 0.038) in lupus nephritis group, respectively.

View Article: PubMed Central - PubMed

ABSTRACT

Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.

The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.

The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0.016), neutrophil gelatinase-associated lipocalin (NGAL) (r = 0.320, P = 0.039), microalbumin (r = 0.621, P = 0.003), transferring (r = 0.451, P = 0.040) levels and renal pathological indices scores, especially interstitial inflammation (r = 0.349, P = 0.025) in active lupus nephritis patients. A significant correlation was found between serum and urine PTX3 levels (r = 0.431, P = 0.006). PTX3 staining was mainly observed in tubulointerstitial areas of patients with lupus nephritis, and immunofluorescence study showed that PTX3 could colocalize with fibroblast in interstitium.

Circulating and local PTX3 levels were significantly increased in patients with active lupus nephritis and might be a biomarker for the disease progression, especially of tubulointerstitial injury.

No MeSH data available.


Related in: MedlinePlus